Topical application of therapeutic agents has received and is presently receiving considerable attention. However, applicants are unaware of any teachings in the prior art of the use of combinations of an antifungal imidazole together with PG or a mixture of PG and IPM or equivalent ester to achieve controlled degrees of penetration of pharmacologically active agents through skin, particularly human skin.
U.S. Pat. No. 4,298,604 which issued on Nov. 3, 1981 describes topical compositions containing the corticosteroid betamethasone dipropionate and, as an antifungal agent, the imidazole derivative, clotrimazole.
European Patent Application 0 270 316 published June 8, 1988 describes topical acne compositions containing 1-substituted imidazole antifungal agents such as tioconazole, clotrimazole, ketoconazole and econazole together with a non-steroidal antiinflammatory agent such as aspirin.
The above identified U.S. patent application Ser. No. 353,890 describes compositions and methods for transdermal penetration of a wide variety of therapeutic agents utilizing topical compositions containing imidazole and certain imidazole derivatives. According to the invention, there is complete penetration of skin with resulting systemic distribution of the therapeutic agent.
U.S. patent application Ser. No. 323,727 also cited above describes topical hydro-alcoholic formulations of 17-ester steroids stabilized in the presence of an antifungal agent such as an imidazole compound. The improvement in stability of 17-ester steroids is claimed to be due to the use of hydro-alcoholic compositions consisting of lower alkanol in combination with dihydroxy alcohol or a trihydroxy alcohol or a mixture thereof gelled with hydroxypropyl or hydroxyethyl cellulose. The application also attributes enhancement of skin penetration of imidazole and 17-ester steroid to lower alkanol such as ethyl alcohol.